Credle Joel J, Gunn Jonathan, Sangkhapreecha Puwanat, Monaco Daniel R, Zheng Xuwen Alice, Tsai Hung-Ji, Wilbon Azaan, Morgenlander William R, Dong Yi, Jayaraman Sahana, Tosi Lorenzo, Parekkadan Biju, Baer Alan N, Roederer Mario, Bloch Evan M, Tobian Aaron A R, Zyskind Israel, Silverberg Jonathan I, Rosenberg Avi Z, Cox Andrea L, Lloyd Tom, Mammen Andrew L, Larman H Benjamin
Institute for Cell Engineering, Division of Immunology, Department of Pathology, Johns Hopkins University School of Medicine; Baltimore, MD, USA.
Institute of Microbiology and Infection, School of Biosciences, University of Birmingham, Edgbaston; Birmingham, United Kingdom.
bioRxiv. 2021 Mar 3:2021.03.02.432977. doi: 10.1101/2021.03.02.432977.
Unbiased antibody profiling can identify the targets of an immune reaction. A number of likely pathogenic autoreactive antibodies have been associated with life-threatening SARS-CoV-2 infection; yet, many additional autoantibodies likely remain unknown. Here we present Molecular Indexing of Proteins by Self Assembly (MIPSA), a technique that produces ORFeome-scale libraries of proteins covalently coupled to uniquely identifying DNA barcodes for analysis by sequencing. We used MIPSA to profile circulating autoantibodies from 55 patients with severe COVID-19 against 11,076 DNA-barcoded proteins of the human ORFeome library. MIPSA identified previously known autoreactivities, and also detected undescribed neutralizing interferon lambda 3 (IFN-λ3) autoantibodies. At-risk individuals with anti- IFN-λ3 antibodies may benefit from interferon supplementation therapies, such as those currently undergoing clinical evaluation.
无偏倚抗体谱分析能够识别免疫反应的靶点。一些可能具有致病性的自身反应性抗体已与危及生命的新冠病毒感染相关联；然而，许多其他自身抗体可能仍不为人知。在此，我们介绍了通过自组装进行蛋白质分子索引（MIPSA）技术，该技术可生成与唯一识别DNA条形码共价偶联的蛋白质开放阅读框文库，以便通过测序进行分析。我们使用MIPSA对55例重症新冠肺炎患者针对人类开放阅读框文库中11,076种DNA条形码标记蛋白质的循环自身抗体进行谱分析。MIPSA识别出了先前已知的自身反应性，还检测到了未描述的中和干扰素λ3（IFN-λ3）自身抗体。具有抗IFN-λ3抗体的高危个体可能会从干扰素补充疗法中获益，比如目前正在进行临床评估的那些疗法。
